体细胞
基因传递
基因
动静脉畸形
载体(分子生物学)
基因表达
细胞
病毒载体
内皮干细胞
基因靶向
病理
生物
血管生成
癌症研究
血管疾病
神经科学
细胞生物学
内皮
医学
中枢神经系统
电池类型
血管
体内
人脑
脑循环
血管畸形
遗传增强
基因表达调控
疾病
生物信息学
慢病毒
免疫学
基因表达谱
组织工程
重组DNA
作者
Jun-Liszt Li,Zhanying Bi,Xing-jun Chen,Tianyue Ming,Baoshan Qiu,Fengzhi Li,Ziyan Feng,Daosheng Ai,Tingting Zhang,Jiayu Wang,Shuai Lin,Yiping Lu,Zhanjing Wang,Juan Huang,Fei Zhao,Hu Zhao,Yilong Wang,Wenzhi Sun,Woo‐Ping Ge
标识
DOI:10.1038/s41551-025-01538-x
摘要
Defects in brain endothelial cells (brainECs) can cause severe cerebrovascular malformations, including arteriovenous malformation (AVM) and cerebral cavernous malformation. The lack of appropriate tools for cerebrovascular disease modelling and local genetic manipulation of the brain vasculature hinders research on cerebrovascular malformations. Here we develop a recombinant adeno-associated virus (rAAV) tool termed miniBEND (rAAV-based mini-system for brain endothelial cells, rAAV-miniBEND), which combines a minimal promoter and an optimized cis-acting element isolated from the mouse gene Tek. This system activates gene expression specifically in mouse and rat brainECs. rAAV-miniBEND achieved high-efficiency and high-specificity gene expression in brainECs through intracranial injection at various developmental stages and through intravenous administration at all postnatal stages in mice. Furthermore, we used rAAV-miniBEND to model sporadic cerebral cavernous malformations mediated by MAP3K3I441M and AVMs mediated by BrafV600E. Somatic expression of BrafV600E in brainECs induced an AVM phenotype, revealing that brainEC proliferation is important for AVM development. Thus, our rAAV-miniBEND system provides a widely applicable tool for cerebrovascular disease modelling and local or global brainEC gene delivery. A recombinant adeno-associated virus system for restricted gene expression in brain endothelial cells enables cerebrovascular disease modelling.
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